Organelle-Specific Thiochromenocarbazole Imide Derivative as a Heavy-Atom-Free Type I Photosensitizer for Biomolecule-Triggered Image-Guided Photodynamic Therapy.
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Saczuk K, Kassem A, Dudek M, Sánchez DP, Khrouz L, Allain M, Welch GC, Sabouri N, Monnereau C, Josse P, Cabanetos C, Deiana M
J Phys Chem Lett 16 (9) 2273-2282 [2025-03-06; online 2025-02-23]
Modern photodynamic therapy (PDT) demands next-generation photosensitizers (PSs) that overcome heavy-atom dependency and enhance efficacy beyond traditional, highly oxygen-dependent type II mechanisms. We introduce herein TCI-NH, as a thiochromenocarbazole imide derivative designed for type I photodynamic action. Upon light activation, TCI-NH efficiently favors superoxide (O2•-) and PS-centered radical formation instead of singlet oxygen (1O2) generation. Its high luminescence efficiency and selective localization in both the endoplasmic reticulum and mitochondria enable precise, image-guided PDT. Notably, interactions with biomolecules, such as serum albumin or DNA, enhance TCI-NH's emission by up to 40-fold and amplify radical generation by up to 5-fold. With negligible dark toxicity, this results in ∼120 nM photocytotoxicity along with an impressive phototherapeutic index exceeding 200. Real-time live-cell imaging revealed rapid, light-triggered cytotoxicity characterized by apoptotic body formation and extensive cellular damage. With its small size, heavy-atom-free structure, exceptional, organelle specificity, and therapeutic efficacy, TCI-NH sets a new benchmark for anticancer type I PDT.
PubMed 39988904
DOI 10.1021/acs.jpclett.5c00136
Crossref 10.1021/acs.jpclett.5c00136